scholarly journals Heterogeneous Nuclear Ribonucleoprotein F Stimulates Sirtuin-1 Gene Expression and Attenuates Nephropathy Progression in Diabetic Mice

Diabetes ◽  
2017 ◽  
Vol 66 (7) ◽  
pp. 1964-1978 ◽  
Author(s):  
Chao-Sheng Lo ◽  
Yixuan Shi ◽  
Isabelle Chenier ◽  
Anindya Ghosh ◽  
Chin-Han Wu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sirtuin 1 ◽  
Diabetic Mice ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Nuclear Ribonucleoprotein ◽  
Heterogeneous Nuclear Ribonucleoprotein F

scholarly journals Insulin Inhibits Nrf2 Gene Expression via Heterogeneous Nuclear Ribonucleoprotein F/K in Diabetic Mice

Endocrinology ◽  
2017 ◽  
Vol 158 (4) ◽  
pp. 903-919 ◽  
Author(s):  
Anindya Ghosh ◽  
Shaaban Abdo ◽  
Shuiling Zhao ◽  
Chin-Han Wu ◽  
Yixuan Shi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Diabetic Mice ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Nuclear Ribonucleoprotein ◽  
Heterogeneous Nuclear Ribonucleoprotein F

scholarly journals Tubular Deficiency of Heterogeneous Nuclear Ribonucleoprotein F Elevates Systolic Blood Pressure and Induces Glycosuria in Mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Chao-Sheng Lo ◽  
Kana N. Miyata ◽  
Shuiling Zhao ◽  
Anindya Ghosh ◽  
Shiao-Ying Chang ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Interstitial Fibrosis ◽  
Sglt2 Inhibitor ◽  
Systemic Hypertension ◽  
Male And Female ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Elevated Systolic Blood Pressure ◽  
Nuclear Ribonucleoprotein ◽  
Heterogeneous Nuclear Ribonucleoprotein F

Abstract We reported previously that overexpression of heterogeneous nuclear ribonucleoprotein F (Hnrnpf) in renal proximal tubular cells (RPTCs) suppresses angiotensinogen (Agt) expression, and attenuates systemic hypertension and renal injury in diabetic Hnrnpf-transgenic (Tg) mice. We thus hypothesized that deletion of Hnrnpf in the renal proximal tubules (RPT) of mice would worsen systemic hypertension and kidney injury, perhaps revealing novel mechanism(s). Tubule-specific Hnrnpf knockout (KO) mice were generated by crossbreeding Pax8-Cre mice with floxed Hnrnpf mice on a C57BL/6 background. Both male and female KO mice exhibited elevated systolic blood pressure, increased urinary albumin/creatinine ratio, tubulo-interstitial fibrosis and glycosuria without changes in blood glucose or glomerular filtration rate compared with control littermates. However, glycosuria disappeared in male KO mice at the age of 12 weeks, while female KO mice had persistent glycosuria. Agt expression was elevated, whereas sodium-glucose co-transporter 2 (Sglt2) expression was down-regulated in RPTs of both male and female KO mice as compared to control littermates. In vitro, KO of HNRNPF in human RPTCs (HK-2) by CRISPR gRNA up-regulated AGT and down-regulated SGLT2 expression. The Sglt2 inhibitor canagliflozin treatment had no effect on Agt and Sglt2 expression in HK-2 and in RPTCs of wild-type mice but induced glycosuria. Our results demonstrate that Hnrnpf plays a role in the development of hypertension and glycosuria through modulation of renal Agt and Sglt2 expression in mice, respectively.

scholarly journals Requirement of Heterogeneous Nuclear Ribonucleoprotein C for BRCA Gene Expression and Homologous Recombination

PLoS ONE ◽  
2013 ◽  
Vol 8 (4) ◽  
pp. e61368 ◽  
Author(s):  
Rachel W. Anantha ◽  
Allen L. Alcivar ◽  
Jianglin Ma ◽  
Hong Cai ◽  
Srilatha Simhadri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Homologous Recombination ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Brca Gene ◽  
Nuclear Ribonucleoprotein

scholarly journals Novel Pathological Role of hnRNPA1 (Heterogeneous Nuclear Ribonucleoprotein A1) in Vascular Smooth Muscle Cell Function and Neointima Hyperplasia

2017 ◽  
Vol 37 (11) ◽  
pp. 2182-2194 ◽  
Author(s):  
Li Zhang ◽  
Qishan Chen ◽  
Weiwei An ◽  
Feng Yang ◽  
Eithne Margaret Maguire ◽  
...  
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Expression Levels ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Atherosclerotic Lesions ◽  
Nuclear Ribonucleoprotein

Objective— hnRNPA1 (heterogeneous nuclear ribonucleoprotein A1) plays a variety of roles in gene expression. However, little is known about the functional involvement of hnRNPA1 in vascular smooth muscle cell (VSMC) function and neointima hyperplasia. In this study, we have attempted to investigate the functional roles of hnRNPA1 in the contexts of VSMC function, injury-induced vessel remodeling, and human atherosclerotic lesions, as well as discern the molecular mechanisms involved. Approach and Results— hnRNPA1 expression levels were consistently modulated during VSMC phenotype switching and neointimal lesion formation induced by wire injury. Functional studies showed that VSMC-specific gene expression, proliferation, and migration were regulated by hnRNPA1. Our data show that hnRNPA1 exerts its effects on VSMC functions through modulation of IQGAP1 (IQ motif containing GTPase activating protein 1). Mechanistically, hnRNPA1 regulates IQGAP1 mRNA degradation through 2 mechanisms: upregulating microRNA-124 (miR-124) and binding to AU-rich element of IQGAP1 gene. Further evidence suggests that hnRNPA1 upregulates miR-124 by modulating miR-124 biogenesis and that IQGAP1 is the authentic target gene of miR-124. Importantly, ectopic overexpression of hnRNPA1 greatly reduced VSMC proliferation and inhibited neointima formation in wire-injured carotid arteries. Finally, lower expression levels of hnRNPA1 and miR-124, while higher expression levels of IQGAP1, were observed in human atherosclerotic lesions. Conclusions— Our data show that hnRNPA1 is a critical regulator of VSMC function and behavior in the context of neointima hyperplasia, and the hnRNPA1/miR-124/IQGAP1 regulatory axis represents a novel therapeutic target for the prevention of cardiovascular diseases.

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